Titration Steps Research Articles

0752 JZP-258 Dose Titration and Transition from Sodium Oxybate in a Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adult Participants With Narcolepsy With Cataplexy

Abstract Introduction Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate (at same concentration as SXB) with 92% less sodium. JZP-258 dose adjustment during titration was evaluated. Methods At study entry, participants were taking SXB only, SXB+other anticataplectics, anticataplectics other than SXB, or were cataplexy treatment-naive. JZP-258 treatment began during a 12-week, open-label optimized treatment and titration period. Participants taking SXB only or SXB+other anticataplectics transitioned to JZP-258 at the same gram-for-gram dose as SXB and titrated to an efficacious and tolerable (optimal) dose from weeks 3-12. Participants taking other anticataplectics or who were anticataplectic-naive initiated JZP-258 at 4.5 g/night and were titrated to an optimal dose at 1-1.5 g/night/week (maximum total dose, 9 g/night). A 2-week stable-dose period and 2-week, double-blind, randomized withdrawal period followed. Results During the stable-dose period, total nightly JZP-258 dose (median [range]) was higher in participants taking SXB at study entry (SXB-only, 7.5 g [4.5-9.0], n=45; SXB+other anticataplectics, 9.0 g [6.0-9.0], n=14) compared with those not taking SXB (other anticataplectics, 7.5 g [4.5-9.0], n=23; anticataplectic-naive, 7.0 g [3.0-9.0], n=67), and dose adjustments were fewer. In most (69%) participants taking SXB at study entry who entered the stable-dose period, no change in dose was required (median [range] number of adjustments was 0 ([0-8]); for those with a change in dose, most changes were within one titration step (1.5 g/night). In participants not taking SXB at study entry, the median (range) number of adjustments was 3.0 (0-7). Conclusion Most participants taking SXB at study entry transitioned to JZP-258 treatment at the same dose with retained effectiveness. Participants not previously taking SXB achieved a tolerable and efficacious dose of JZP-258 after a median of 3 adjustments. Support Jazz Pharmaceuticals

Concentration gradient Co–Fe nanowire arrays: Microstructure to magnetic characterizations

Abstract In the present investigation, systematic method to fabricate nanowire arrays with a linear gradient of cobalt-iron composition has been reported. The nanowires were fabricated by direct current (DC) electro-deposition following a multi-step titration method into a commercial anodic aluminium oxide (AAO) template. Nearly 100% gradient of Co and Fe content in the nanowires is achieved following the present method. The gradient of Co and Fe composition along the nanowires is established by Energy-dispersive X-ray (EDX) mapping in scanning electron microscope (SEM). The results from EDX mapping are further supported by the microstructural characterization along the wire axis using high resolution transmission electron microscope (HRTEM) images and SAED pattern. The microstructural characterization reveals variation of crystalline phases that are signature of Co and Fe content along the wires. To explore the magnetization dynamics of nanowire arrays, ferromagnetic resonance (FMR) study was performed in flip-chip geometry. The FMR study shows the presence of four well-separated resonance peaks in gradient nanowires which is a unique finding in the present investigation. A detailed FMR analysis has been presented to reveal the origin of these peaks. The values of the Gilbert damping parameter, obtained from the FMR linewidth analysis establish the correlation of FMR response with the average composition of Co–Fe in nanowires, grown in each step of titration. This study highlights the necessity of the detailed investigation of microstructures and magnetization dynamics of gradient ferromagnetic nanowire arrays that are emerging in high-frequency spintronics applications, more suitable for a tunable tri-band band-pass filter.

Introduction of sacubitril/valsartan in primary care follow-up of heart failure: a prospective observational study (THESEUS).

AimsSwitch from angiotensin converting enzyme inhibitor treatment to sacubitril/valsartan (sac/val) is associated with benefit in heart failure with reduced ejection fraction (HFrEF). Reports on management of this switch are largely based on randomized controlled trials, retrospective analyses, and hospital‐based care, while patients with chronic heart failure (CHF) are frequently followed‐up in primary care. The THESEUS study aimed to characterize the transition to sac/val and early maintenance period of HFrEF in primary care.Method and resultsTHESEUS was a prospective, observational, non‐interventional study, performed at primary care sites throughout Switzerland. Patient characteristics, sac/val transition, and maintenance were reported at study enrolment and approximately 3 and 6 months after sac/val initiation. The primary endpoint was achievement of 200 mg BID sac/val with maintenance for ≥12 weeks. Secondary outcomes included dosing regimens, healthcare utilization in the 6 months prior to sac/val initiation and during the study, patient well‐being, safety, and tolerability. Fifty‐eight patients with CHF were enrolled from 45 primary care centres. Six patients were excluded, and 19 achieved the primary endpoint (36.5%, Achievers). Non‐Achievers underwent fewer titration steps than Achievers (1.9 ± 0.9 vs. 3.1 ± 1.4). In both groups, patient well‐being improved and the percentage of New York Heart Association III patients decreased. Healthcare utilization decreased (19% vs. 30.8% in the 6 months pre‐enrolment period). The most frequent reasons for target dose non‐achievement were asymptomatic and symptomatic hypotension (15.3% and 12.1%, respectively).ConclusionsResults from THESEUS suggest that transition to sac/val is manageable in primary care, with a safety profile corresponding to reports from specialized heart failure care.

Rationale and design of a navigator-driven remote optimization of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

Although optimal pharmacological therapy for heart failure with reduced ejection fraction (HFrEF) is carefully scripted by treatment guidelines, many eligible patients are not treated with guideline‐directed medical therapy (GDMT) in clinical practice. We designed a strategy for remote optimization of GDMT on a population scale in patients with HFrEF leveraging nonphysician providers. An electronic health record‐based algorithm was used to identify a cohort of patients with a diagnosis of heart failure (HF) and ejection fraction (EF) ≤ 40% receiving longitudinal follow‐up at our center. Those with end‐stage HF requiring inotropic support, mechanical circulatory support, or transplantation and those enrolled in hospice or palliative care were excluded. Treating providers were approached for consent to adjust medical therapy according to a sequential, stepped titration algorithm modeled on the current American College of Cardiology (ACC)/American Heart Association (AHA) HF Guidelines within a collaborative care agreement. The program was approved by the institutional review board at Brigham and Women's Hospital with a waiver of written informed consent. All patients provided verbal consent to participate. A navigator then facilitated medication adjustments by telephone and conducted longitudinal surveillance of laboratories, blood pressure, and symptoms. Each titration step was reviewed by a pharmacist with supervision as needed from a nurse practitioner and HF cardiologist. Patients were discharged from the program to their primary cardiologist after achievement of an optimal or maximally tolerated regimen. A navigator‐led remote management strategy for optimization of GDMT may represent a scalable population‐level strategy for closing the gap between guidelines and clinical practice in patients with HFrEF.

Effect of Stress on Li Transport in High Energy Density Electrode Materials

Solid-state diffusion of lithium through the active material is a crucial aspect of lithium-ion battery operation. Quantitative analysis of transport properties is important to understand diffusion mechanisms and designing effective electrode architectures for Li-ion battery. There is a large body of literature exists on Li diffusion coefficient measurement techniques in various electrodes, among them, galvanostatic intermittent titration technique (GITT) and the potentiostatic intermittent titration technique (PITT) are the most widely used methods. However, none of the existent studies considered electrode stresses and the effect of stresses on the measured chemical diffusion coefficient. In this study, sputter deposited Ge films (as a model high energy electrode material) were subjected to potentiostatic intermittent titration technique (PITT) and galvanostatic intermittent technique (GITT) conditions while simultaneously measuring the stress evolution in the electrodes. It was observed that the stresses varied significantly in a single titration step during GITT experiment, which violates the assumptions of Fickian transport model where the electrode stresses are usually neglected. Therefore, only PITT data was analyzed to obtain the chemical diffusion coefficient of Li in Ge. As expected, the diffusion coefficient value increased considerably with Li concentration; however, the values obtained during delithiation are at least two times higher than those obtained during lithiation at any given concentration, with the difference becoming significantly higher with Li concentration. This difference is attributed to the state of stress, i.e., tensile state of stress enhances diffusion and compressive state of stress impedes the diffusion process. The data and observations presented here will be helpful in developing and using electro-chemo-mechanical models in producing optimized electrode microstructures.

Rapid titration protocol – Experiences with a dynamic novel titration regime for vagus nerve stimulation in a group of depressive patients

Vagus nerve stimulation (VNS) is an established tool in the psychiatric armamentarium for patients with therapy-resistant depression (TRD) with response rates of approximately 60%. So far, VNS is titrated slowly during ambulatory in-office visits. Thus, antidepressive effects can be expected after approximately six months.We report our experiences with a rapid dosing regime (RDR) with titration start shortly after VNS-implantation. We retrospectively analysed data of six patients with TRD who received VNS. Stimulation parameters were evaluated with regard to clinical side effects, heart rates (HR) and blood pressures (BP). Depressive symptoms were measured by Montgomery-Asberg Depression Rating Scale (MADRS) one week before and three months after implantation of the VNS.All patients received first stimulation between one and four days after surgery. We elevated output current using 0.25 mA titration steps. We increased output current between one and four days after the last titration. All patients received 1.0 mA output current after eight to 14 days post-surgery. HR and BP remained stable in all patients. All side effects were mild and temporary. MADRS scores were significantly lower three months after VNS-implantation (24 ± 8) than one week before VNS-implantation (42 ± 4; p = 0.028).The therapeutic range of VNS-parameters for antidepressive effect was reached quicker without finding increased numbers of side effects. Consequently, by using RDR the antidepressive effect of VNS-therapy for patients with TRD could be reached earlier than using slow titration. Our presented RDR might be able to significantly shorten the “clinical effect gap” due to the neurobiological and titration-related latency.

Safety and Tolerability of Initiating Maximum-Dose Sacubitril-Valsartan in Patients on Target Dose Renin-Angiotensin System Inhibitors.

Aim Sacubitril-valsartan has proven beneficial in heart failure with reduced ejection fraction. Guidelines recommend initiating half-dose sacubitril-valsartan before up-titration even to patients already on target dose angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). To reduce the number of titration steps needed in order to simplify for the patient as well as the clinic, we aimed to investigate the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan. Methods This prospective cohort study was conducted between April 2016 and November 2017. A total of 66 patients with heart failure and reduced ejection fraction already on guideline-recommended target dose ACE inhibitors or ARBs (equivalent to enalapril 10 mg twice daily) were switched to maximum-dose sacubitril-valsartan (200 mg twice daily). The patients were followed for twelve months. Results Patients had a mean age of 72 ± 10 years, mean systolic blood pressure of 121 ± 17 mmHg, and 92% were male. At 12-month follow-up, nine patients (14%) had discontinued sacubitril-valsartan, four patients (6%) had a dose reduction, and 17 patients (26%) had developed symptomatic hypotension. No angioedema occurred within the 12-month follow-up and there were no hospitalizations or emergency room visits within the first 14 days. ConclusionsSwitching directly from target dose ACE inhibitors or ARBs to maximum-dose sacubitril-valsartan was safe and generally well tolerated.

A facile and tunable approach for synthesis of pure silica nanostructures from rice husk for the removal of ciprofloxacin drug from polluted aqueous solutions

We herein have developed a simple and economical approach for the synthesis of pure SiO2 nanoparticles from rice husk. Accordingly, the rice husk was acid-leached, and silica was subsequently extracted with 2 M sodium hydroxide solution. The silica gel was then precipitated by titration of the extract with sulfuric or nitric acid until pH reached 4, 5, or 7. The results evidenced that the sequence of addition of the acids (required for acid-leaching and titration steps), calcination temperature, and pH of the titrated media played an essential role for tuning the phase purity, yield, and crystallite size of the synthesized SiO2 nanoparticles. The products were elucidated by XRD, FE-SEM, TEM, EDS, FT-IR, BET, and thermal analysis techniques. The optimized conditions: HNO3 and H2SO4 acid sequence addition, pH 7, and 600 or 800 °C calcination temperature, produced pure amorphous SiO2 or SiO2 nanostructure with 14 nm average crystallite size. The produced SiO2 products showed good adsorption capacity (ca. 190 and 30 mg/g) for the removal of ciprofloxacin (CIP) drug from aqueous solutions. As such, various factors influencing the adsorption process were examined. The adsorption results fitted well the pseudo-second-order kinetic and Langmuir isotherm models. The determined thermodynamic constants (ΔHo = 9.9 4 kJ/mol, ΔGo = −19.55 kJ/mol, and Ea = 27.24 kJ/mol) exhibited that the adsorption of CIP drug using the as-prepared SiO2 nano-adsorbent was an endothermic, physisorption, and spontaneous process. The present investigation demonstrated that the SiO2 nano-adsorbent is a good candidate for the removal of CIP drug from the environmentally polluted water.

Auditing the Efficacy and Safety of Alfacalcidol and Calcium Therapy in Idiopathic Hypoparathyroidism.

Patients with hypoparathyroidism are treated with vitamin D and calcium. PTH is an emerging option because of its physiological action. It is important to assess the efficacy and shortcomings of conventional therapy. We assessed the efficacy and safety of alfacalcidol in a large cohort of patients with idiopathic hypoparathyroidism (IH) and identified a subset who could be treated without oral calcium. Observational study at tertiary care center. We assessed 92 patients with IH who were receiving alfacalcidol and oral calcium to maintain an optimal serum total calcium level of 8.0 to 8.5 mg/dL during routine follow-up. Patients with suboptimal control were provided free medicines and followed up frequently. Oral calcium and alfacalcidol doses were titrated sequentially to determine the minimum doses for optimal calcium control. Serum phosphate level, 1,25-dihydroxyvitamin D, fractional excretion of phosphorus (FEPh), and hypercalciuria (urine calcium-to-creatinine ratio, >0.2) were assessed at each step of titration. Only 38% of patients had optimal calcium control during routine follow-up. With good compliance, all achieved optimal serum calcium and 1,25-dihydroxyvitamin D levels and 43% of patients could stop taking oral calcium. Hyperphosphatemia, hypercalciuria, and low FEPh persisted at all stages of therapy. Serum phosphorus levels normalized when the serum calcium level increased to 9.9 mg/dL, but this level of serum total calcium was associated with hypercalciuria in 90% of patients. Alfacalcidol is effective in achieving calcemic control in IH. Calcemic control without oral calcium was achieved in 43% of patients receiving alfacalcidol. However, optimal calcium control was associated with hyperphosphatemia and hypercalciuria in most patients.

Bivalirudin and ECLS

Bivalirudin and ECLS

Navigator-Driven Remote Optimization of Guideline-Directed Medical Therapy in Patients with Heart Failure with Reduced Ejection Fraction: Program Design and Initial feasibility

Introduction Although optimal pharmacological therapy for heart failure with reduced ejection fraction (HFrEF) is carefully scripted by treatment guidelines, many eligible patients are not treated with guideline-directed medical therapy (GDMT) in clinical practice. We designed a strategy for remote optimization of GDMT on a population scale in patients with HFrEF leveraging non-physician providers. A navigator-led remote medication optimization program will enhance implementation of GDMT in HFrEF patients. Methods An electronic health record-based algorithm was used to identify a cohort of patients with a diagnosis of HF and EF ≤ 40% receiving longitudinal follow up at our center. Those with end-stage HF requiring inotropic support, mechanical circulatory support, or transplantation and those enrolled in hospice or palliative care were excluded. Treating providers were approached for consent to adjust medical therapy according to a sequential, stepped titration algorithm modelled on the current ACC/AHA HF Guidelines. A navigator then facilitated medication adjustments by telephone and conducted longitudinal surveillance of laboratories, blood pressure, and symptoms. Each titration step was reviewed by a pharmacist under supervision of a nurse practitioner and HF cardiologist. Patients were discharged from the program to their primary cardiologist after achievement of an optimal or maximally tolerated regimen. (Figure). Results To date, 615 HFrEF patients have been initially screened for eligibility, of whom 197 (32%) were deemed suitable for remote medication optimization. Further chart review determined 11 (6%) of these patients were already optimized by guidelines. Cardiologists for the remaining 186 patients were approached; provider consent was received for 145 patients (78%). Of these 145 patients, 13 (9%) declined participation, 13 (9%) were unreachable by telephone, and the remaining 119 have been enrolled. Conclusion A navigator-led remote management strategy for optimization of GDMT is feasible for a large proportion of patients with HFrEF and appears acceptable to the vast majority of patients and providers. This approach may represent a scalable population-level strategy for closing the gap between guidelines and clinical practice in patients with HFrEF.

Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis.

Vancomycin is a key antibiotic used in the treatment of multiple conditions including infections associated with cystic fibrosis and methicillin-resistant Staphylococcus aureus. The present study sought to develop a model based on empirical evidence of optimal vancomycin dose as judged by clinical observations that could accelerate the achievement of desired trough level in children with cystic fibrosis. Transformations of dose and trough were used to arrive at regression models with excellent fit for dose based on weight or age for a target trough. Results of this study indicate that the 2 proposed regression models are robust to changes in age or weight, suggesting that the daily dose on a per-kilogram basis is determined primarily by the desired trough level. The results show that to obtain a vancomycin trough level of 20 μg/mL, a dose of 80 mg/kg/day is needed. This analysis should improve the efficiency of vancomycin usage by reducing the number of titration steps, resulting in improved patient outcome and experience.

In Situ Measurement of the Effect of Stress on the Chemical Diffusion Coefficient of Li in High-Energy-Density Electrodes

Sputter deposited germanium thin films were assembled in a half-cell configuration with lithium foil as counter/reference electrode and 1M LiPF6 in EC, DEC, DMC solution (1:1:1, wt%) as electrolyte. The Ge films were subjected to potentiostatic intermittent titration technique (PITT) and galvanostatic intermittent technique (GITT) conditions while simultaneously measuring the stress evolution in the electrodes. It was observed that the electrode stresses varied significantly in a single titration step during a GITT experiment, which violates the assumptions of simple Fickian transport model where the electrode stresses are usually neglected. Therefore, only the PITT data was analyzed to obtain the chemical diffusion coefficient of Li in Ge. As expected, the diffusion coefficient value increased considerably with Li concentration; however, the values obtained during delithiation are at least two times greater than those obtained during lithiation at any given Li concentration, with the difference becoming significantly higher at higher Li concentration. This difference is attributed to the stress state, i.e., tensile stress during delithiation leads to higher values compared to the compressive stresses during lithiation. The data and observations presented here will be helpful in developing and using electrochemomechanical models in producing optimized electrode microstructures.

Colorimetric determination of acidity constant using a paper-based microfluidic analytical device

Acid dissociation constant is an important chemical characteristic of organic and inorganic compounds and it affects both chemical properties and biological activities of the molecules. Herein, a very simple, fast and cost-effective method based on microfluidic technology has been reported for colorimetric determination of acidity constants. The designed device works based on pH-metric titration of colorful indicators followed by colorimetric measurements by a smart phone mobile device or a flatbed scanner. So, it does not need sophisticated instrumentation and is accomplished in a very short time (about 1 min). All titration steps are transferred on a star-like designed µPAD device: (1) spotting 0.3 µL buffers of different pHs at the end of the channels (reaction zones), (2) spotting a 30 µL portion of the indicator on the center of µPAD followed by movement of indicator solution toward the reaction zone by capillary action of the paper. The measured color change of the indicators at the reaction zone is fitted to the Henderson–Hasselbalch equation, through which acidity constants are calculated. The performance of the device was evaluated by measuring acidity constant of 4 indicators including bromothymol blue, bromocresol green, bromocresol purple and phenolphthalein. A very close agreement was achieved between those measured by the suggested device here and the previously reported values. The reproducibility of this method was lower than 5% for relative standard deviation of three replicate measurements.

New analytical methodology for analysing S(IV) species at low pH solutions by one stage titration method (bichromatometry) with a clear colour change. Could potentially replace the state-of-art-method iodometry at low pH analysis due higher accuracy.

A new, faster and more reliable analytical methodology for S(IV) species analysis at low pH solutions by bichromatometry is proposed. For decades the state of the art methodology has been iodometry that is still well justified method for neutral solutions, thus at low pH media possess various side reactions increasing inaccuracy. In contrast, the new methodology has no side reactions at low pH media, requires only one titration step and provides a clear color change if S(IV) species are present in the solution. The method is validated using model solutions with known concentrations and applied to analyses of gaseous SO2 from purged solution in low pH media samples. The results indicate that bichromatometry can accurately analyze SO2 from liquid samples having pH even below 0 relevant to metallurgical industrial processes.

A convenient method for phase separation and composition determination of the Bunsen reaction products in sulfur-iodine hydrogen production process

During the integrated operation of the sulfur-iodine process, it is important to conveniently and quickly measure the composition of the Bunsen reaction products and to ascertain the location of each phase in the liquid–liquid phase separator. First, the method to determine each composition in HIx phase system which contains four components of HI, I2, H2O, and H2SO4 was newly proposed using only the data of H+ and I− contents and the density of the HIx phase. This method has the advantage to replace the complicated and time-consuming traditional titration step of I2. The calculated I2/HI molar ratios were within an error of ±5% at all temperature conditions, indicating that this method was suitable for I2 composition analysis. Meanwhile, the use of an electrical conductivity sensor was discussed as a sensing technology during the phase separation of Bunsen reaction products. The electrical conductivity was measured using different compositions of the Bunsen reaction products. The conductivity difference between H2SO4 and HIx phase solutions was approximately 478–822 mS/cm in the main compositional range of the Bunsen reaction products. Therefore, this method can replace the traditional phase separation method using a DP (differential pressure) cell.

Protein Nitrogen Determination by Kjeldahl Digestion and Ion Chromatography

We report development and validation of a simple, rapid, and accurate method for the quantitation of protein nitrogen, which combines Kjeldahl digestion and ion chromatography with suppressed conductivity detection and requires nanomolar amount of nitrogen in samples (≥10 μg protein). The mechanism of suppressed conductivity detection does not permit analysis of samples containing copper (present in Kjeldahl digestion solution) and aluminum (present in many vaccines as adjuvants) due to precipitation of their hydroxides within the suppressor. We overcame this problem by including 10 μM oxalic acid in Kjeldahl digests and in the eluent (30 mM methanesulfonic acid). The chromatography is performed using an IonPac CS-16 cation exchange column by isocratic elution. The method reduces the digestion time to less than 1 h and eliminates the distillation and titration steps of the Kjeldahl method, thereby reducing the analysis time significantly and improving precision and accuracy. To determine protein nitrogen in samples containing non-protein nitrogen, proteins are precipitated by a mixture of deoxycholate and trichloroacetic acid and the precipitates are analyzed after dissolving in KOH. The method is particularly useful for biological samples that are limited and can also be applied to food, environmental, and other materials.

SoC dependent kinetic parameters of insertion electrodes from staircase — GITT

A staircase galvanostatic intermittent titration technique (SC-GITT) is introduced and exemplarily examined using the well-known half-cell reaction, LiCoO2 | Li. SC-GITT expands the common GITT and complements the number of accessible kinetic parameters by the ohmic resistance, the exchange current density and the charge transfer coefficient. In contrast to conventional GITT, the magnitude of the applied current is rapidly varied in a staircase like manner previously to the actual titration step. The overpotentials obtained within the staircase regime are fitted to a modified Butler–Volmer equation to determine the kinetic parameters. In the case of LiCoO2, the results reveal a significant lithium concentration dependence of the charge transfer kinetics and the ohmic resistance. The proposed experimental technique appears to be well suited for the investigation of electrochemical kinetics for all kinds of insertion electrodes.

Employing a step-wise titration method under semi-slow reaction regime for evaluating the reactivity of limestone and dolomite in acidic environment

Carbonate rocks are commonly utilized in Wet Flue Gas Desulfurization, WFGD, because of their capability to release calcium ions and precipitate as solid gypsum in an acidic environment. Studies on the reactivity of carbonate rocks and dissolution models can be employed for optimizing the WFGD process. The correct evaluation of limestone reactivity is therefore necessary for the design of the WFGD scrubbing process and for plant operation. In this study, after statistical considerations on evaluating the sample size threshold, a mathematical model and a detailed procedure are given for the estimation of the reaction rate constant and mass transfer coefficient.Results are reported from testing limestone and dolomite samples with different formation periods and geological backgrounds. Samples were tested in a Batch Stirred Tank Reactor (BSTR) with a stepwise titration method using hydrochloric acid and non-steady state conditions. In the experiments particles were shown to be completely immersed in a defined viscous sub-layer. A parametric evaluation for the reaction rate was performed at each titration step using an implemented software procedure that handles hundreds of pH values and more than fifty particle size ranges. The experimental data were accurately fitted to the model. The second order model for dolomite and limestone samples accounts for both mass transfer and reaction rate terms, yielding values for the mass transfer coefficients that are congruent with values estimated by fluid-dynamics inspection.

Combination of a Copper-Ion Selective Electrode and Fluorometric Titration for the Determination of Copper(II) Ion Conditional Stability Constants of Humic Substances.

A fluorescence quenching model using copper(II) ion (Cu(2+)) ion selective electrode (Cu-ISE) is developed. It uses parallel factor analysis (PARAFAC) to model fluorescence excitation-emission matrices (EEMs) of humic acid (HA) samples titrated with Cu(2+) to resolve fluorescence response of fluorescent components to Cu(2+) titration. Meanwhile, Cu-ISE is employed to monitor free Cu(2+) concentration ([Cu]) at each titration step. The fluorescence response of each component is fit individually to a nonlinear function of [Cu] to find the Cu(2+) conditional stability constant for that component. This approach differs from other fluorescence quenching models, including the most up-to-date multi-response model that has a problematic assumption on Cu(2+) speciation, i.e., an assumption that total Cu(2+) present in samples is a sum of [Cu] and those bound by fluorescent components without taking into consideration the contribution of non-fluorescent organic ligands and inorganic ligands to speciation of Cu(2+). This paper employs the new approach to investigate Cu(2+) binding by Pahokee peat HA (PPHA) at pH values of 6.0, 7.0, and 8.0 buffered by phosphate or without buffer. Two fluorescent components (C1 and C2) were identified by PARAFAC. For the new quenching model, the conditional stability constants (logK1 and logK2) of the two components all increased with increasing pH. In buffered solutions, the new quenching model reported logK1 = 7.11, 7.89, 8.04 for C1 and logK2 = 7.04, 7.64, 8.11 for C2 at pH 6.0, 7.0, and 8.0, respectively, nearly two log units higher than the results of the multi-response model. Without buffer, logK1 and logK2 decreased but were still high (>7) at pH 8.0 (logK1 = 7.54, logK2 = 7.95), and all the values were at least 0.5 log unit higher than those (4.83 ~ 5.55) of the multi-response model. These observations indicate that the new quenching model is more intrinsically sensitive than the multi-response model in revealing strong fluorescent binding sites of PPHA in different experimental conditions. The new model was validated by testing it with a mixture of two fluorescing Cu(2+) chelating organic compounds, i.e., l-tryptophan and salicylic acid mixed with one non-fluorescent binding compound oxalic acid titrated with Cu(2+) at pH 5.0.